1. Integrin (αvβ3) Targeted RGD Peptide Based Probe for Cancer Optical Imaging
Meihui Liu, Wenbin Zeng, Lun Yu, Zhiguo Liu, Xintong Zhang, Xiaobo Wang Curr Protein Pept Sci . 2016;17(6):570-81. doi: 10.2174/1389203717666160101124015.
Integrins have an important impact on the regulation of normal and tumor cell migration and survival, especially the integrin αvβ3 and its role in angiogenesis and tumor metastasis. Owing to the role of integrins, non-invasive imaging of αvβ3 expression in diseased tissue will be of great benefit in directing adjuvant therapy for cancer patients. To this end, RGD peptide based probes for optical imaging have emerged as a real-time, sensitive, and noninvasive approach for visualization, localization, and measurement of cancer in vivo. With the advantages of optical imaging such as sensitivity, cost effectiveness, and non-invasion, the past decades have witnessed the rapid development of integrin- targeted optical probes and its wide applications in cancer research. In this review, we present and introduce numerous approaches by the term "RGD motif based optical imaging probes" with respect to their probe design strategies and applications. Additionally, a variety of labels such as QDs, UCLs and near-infrared fluorochrome used in these optical imaging probes are also discussed.
2. RGD peptide grafted polybutylene adipate- co-terephthalate/gelatin electrospun nanofibers loaded with a matrix metalloproteinase inhibitor drug for alleviating of wounds: an in vitro/ in vivo study
Nasim Sarrami, Emadeddin Yazdani Kachouei, Jaleh Varshosaz, Monireh Kouhi, Ali Jahanian-Najafabadi, Khatereh Arabloo, Erfaneh Ghassami Drug Dev Ind Pharm . 2020 Mar;46(3):484-497. doi: 10.1080/03639045.2020.1730397.
The objective of the present study was the fabrication of a wound dressing membrane based on RGD modified polybutylene adipate-co-terephthalate (PBAT)/gelatin nanofibrous structures loaded with doxycycline (DOX). This type of nanofiber for wound healing has not been reported so far and is quite novel. PBAT and gelatin nanofibers were separately electrospun using double needles electrospinning setup. Electrospinning variables were optimized to obtain bead-free thin nanofibers. The amount of drug loaded and release were measured in different concentrations of DOX and PBAT. MMPs inhibition was studied by polyacrylamide gel-zymography. Then, surface of the nanofibers was modified with RGD peptide, and their antimicrobial effect was investigated onStaphylococcus aureusandPseudomonas aeruginosa. Effect of developed nanofibrous membranes on L929 fibroblast cells proliferation, adhesion and closure of excised wounds in rat were also studied. PBAT/gelatin nanofibrous structures with average fiber diameter of 75-529 nm were developed successfully. Drug release study revealed that about 65% of DOX was released from the optimized formulation (P17D1.6) after 20 h. The developed DOX loaded membrane inhibited the MMPs activity and showed no cytotoxicity. RGD surface-modified PBAT/gelatin nanofibers significantly improved the wound closure and histopathological results (re-epithelialization, collagen deposition, and angiogenesis) in rats compared to the control groups. Overall, RGD immobilized PBAT/gelatin nanofibrous membrane may have a potential application for wound healing.
3. Inhibited effect of an RGD peptide hydrogel on the expression of β1-integrin, FAK, and Akt in Tenon's capsule fibroblasts
Zheng Wang, Chenchen Zhao, Liye He, Baoji Chen, Ping Wu, Na Xu, Ran Zhang, Liang Liang J Biomed Mater Res B Appl Biomater . 2021 Nov;109(11):1857-1865. doi: 10.1002/jbm.b.34847.
Tenon's capsule fibroblasts are the main cellular components of filtration tract scar that limit the success rate of glaucoma filtration surgery. Scar formation results from infiltration and proliferation of fibroblasts into damaged areas, meanwhile synthesis of extracellular matrix glycoproteins. Integrins are cell surface receptors for extracellular molecules that mediate cell adhesion, spreading, migration, and invasion. They bind their ligands often through recognition of short amino-acid sequences-arginine-glycine-aspartic acid (RGD). Peptides that contain RGD sequence can compete with RGD containing insoluble matrix proteins for binding to the integrin receptor and thus prevent the downstream signaling pathway. Increasing evidence supports that β1-integrin/focal adhesion kinase (FAK)/Akt signal pathway plays an important role in fibrogenesis and scar formation in different tissues. In consideration of advantages of peptide hydrogel, that is well biocompatibility, gel state, degradability, good drug loading, we designed and fabricated an RGD peptide hydrogel, and hypothesized that it could inhibit the expression of β1-integrin, FAK, and Akt in Tenon's capsule fibroblasts. Rheology results showed that 1% wt Fmoc-FFGGRGD peptide solution could self-assemble into hydrogel. Western blot analysis revealed that there were statistical differences between control group and 1% wt group in β1-integrin/β-actin, FAK/β-actin, Akt/β-actin respectively (*p < .05). The relative mRNA expression of β1-integrin, FAK, Akt in control group and 1% wt group were also statistically different respectively (*p < .05). We proved that 1% wt Fmoc-FFGGRGD self-assembly peptide hydrogel could inhibit the expression of β1-integrin, FAK and Akt in Tenon's capsule fibroblasts. It is a promising way to solve scar formation of glaucoma filter channel.
